PMID- 34773653 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220531 IS - 1600-0765 (Electronic) IS - 0022-3484 (Linking) VI - 57 IP - 1 DP - 2022 Jan TI - Activation of GATA-binding protein 4 regulates monocyte chemoattractant protein-1 and chemotaxis in periodontal ligament cells. PG - 195-204 LID - 10.1111/jre.12953 [doi] AB - BACKGROUND AND OBJECTIVES: Periodontitis is a chronic inflammatory disease of periodontal supporting tissues. The persistent inflammatory reaction depends on the release of chemokines to continuously recruit inflammation cells. GATA-binding protein 4 (GATA4) exerts effects on senescence and inflammation, while its role in periodontitis is far from clear. The present study aims to address the effect of GATA4 on regulating chemokines and the chemotaxis in periodontitis. MATERIAL AND METHODS: Periodontitis rat models were constructed to detect the expression of GATA4 and the chemokine monocyte chemoattractant protein-1 (MCP-1) by immunohistochemistry. Lipopolysaccharide (LPS)-stimulated human periodontal ligament (PDL) cells and GATA4-knockdown by siRNA transient transfection PDL cells were used to explore the correlation between GATA4 and chemokines. Transwell assay was performed to detect the role of GATA4 for the recruitment effect of chemokines on macrophages. Mitogen-activated protein kinase (MAPK) inhibitors were scheduled to intervene in LPS-stimulated PDL cells to examine the association between MAPK signaling pathways and GATA4. The expression of GATA4, chemokines, or MAPK signaling molecules was determined by quantitative real-time polymerase chain reaction, western blotting, or cell immunofluorescence. RESULTS: The expression of GATA4 and MCP-1 was significantly increased in periodontitis rat models and in LPS-stimulated PDL cells. Knockdown GATA4 inhibited the expression of GATA4 and MCP-1 as well as suppressed the recruitment of macrophage in LPS-stimulated PDL cells. Inhibitors of p38 and ERK1/2 signaling pathways significantly downregulated the increased expression of GATA4 and MCP-1 induced by LPS in PDL cells. CONCLUSIONS: GATA-binding protein 4 could act as an upstream regulator of MCP-1 and as a downstream regulator of p38 and ERK1/2 signaling pathways to initiate inflammation response and regulate chemotaxis during the progression of periodontitis. CI - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Zhu, Ningjing AU - Zhu N AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. FAU - Zheng, Xueqing AU - Zheng X AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. FAU - Qiao, Weiwei AU - Qiao W AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. FAU - Huang, Wushuang AU - Huang W AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. FAU - Li, Ruiqi AU - Li R AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. FAU - Song, Yaling AU - Song Y AUID- ORCID: 0000-0003-0747-7381 AD - The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei_MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. LA - eng GR - 81670976/National Natural Science Foundation of China/ GR - [2014]160/Bureau of Science and Technology of Wuhan/ PT - Journal Article DEP - 20211113 PL - United States TA - J Periodontal Res JT - Journal of periodontal research JID - 0055107 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (GATA4 Transcription Factor) RN - 0 (Gata4 protein, rat) RN - 0 (Lipopolysaccharides) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cells, Cultured MH - *Chemokine CCL2/genetics/metabolism MH - *Chemotaxis MH - GATA4 Transcription Factor/*metabolism MH - Lipopolysaccharides MH - *Periodontal Ligament/cytology MH - Rats MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism OTO - NOTNLM OT - GATA4 OT - MAPK signaling pathways OT - MCP-1 OT - chemotaxis OT - periodontitis EDAT- 2021/11/14 06:00 MHDA- 2022/01/19 06:00 CRDT- 2021/11/13 12:12 PHST- 2021/10/14 00:00 [revised] PHST- 2021/09/15 00:00 [received] PHST- 2021/10/30 00:00 [accepted] PHST- 2021/11/14 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2021/11/13 12:12 [entrez] AID - 10.1111/jre.12953 [doi] PST - ppublish SO - J Periodontal Res. 2022 Jan;57(1):195-204. doi: 10.1111/jre.12953. Epub 2021 Nov 13.